Safety and Efficacy of Long-Term Co-Administration of Fenofibrate and Ezetimibe in Patients With Mixed Hyperlipidemia

doi:10.1016/j.jacc.2005.11.072

Journal of the American College of Cardiology

Volume 47, Issue 8, 18 April 2006, Pages 1584-1587

https://doi.org/10.1016/j.jacc.2005.11.072 Get rights and content

Under an Elsevier user license

open archive

Objectives

This study sought to determine the long-term safety and efficacy of co-administered fenofibrate (FENO) and ezetimibe (EZE) in patients with mixed hyperlipidemia.

Background

Both EZE and FENO offer complementary benefits to the lipid profile of patients with mixed hyperlipidemia.

Methods

After completing the 12-week randomized, double-blind base study that compared EZE 10 mg, FENO 160 mg, FENO 160 mg plus EZE 10 mg, and placebo in patients with mixed hyperlipidemia, patients continued into a double-blind, 48-week extension phase. Those patients in the FENO plus EZE and FENO groups continued on their respective base study treatment, and patients in the EZE and placebo groups were switched to FENO plus EZE and FENO, respectively.

Results

Of the 587 patients who completed the base study, 576 continued into the extension study (n = 340 in FENO plus EZE and n = 236 in FENO). The FENO plus EZE produced significantly greater reductions in low-density lipoprotein-cholesterol compared with FENO (−22% vs. −9%, respectively; p < 0.001). There were also significantly greater improvements in triglycerides, high-density lipoprotein cholesterol (HDL-C), total cholesterol, non–HDL-C, and apolipoprotein B with FENO plus EZE compared with FENO. Changes in apolipoprotein A-I and high-sensitivity C-reactive protein were similar between groups. Overall, FENO plus EZE was well tolerated during the extension study. The proportion of patients with consecutive elevations of alanine aminotransferase/aspartate aminotransferase ≥3 times upper limit of normal were similar between the FENO plus EZE (1.2%) and FENO (1.7%) groups. No cases of creatine phosphokinase elevations ≥10 times upper limit of normal or myopathy were observed in either group.

Conclusions

Long-term, 48-week co-administration of FENO plus EZE was well tolerated and more efficacious than FENO in patients with mixed hyperlipidemia.

Abbreviations and Acronyms

adverse experience

ALT

alanine aminotransferase

AST

aspartate aminotransferase

CPK

creatine phosphokinase

EZE

ezetimibe

FENO

fenofibrate

HDL-C

high-density lipoprotein-cholesterol

hs-CRP

high-sensitivity C-reactive protein

LDL-C

low-density lipoprotein-cholesterol

total cholesterol

ULN

upper limit of normal

Cited by (0)

: This study was funded by Merck/Schering-Plough Pharmaceuticals, North Wales, Pennsylvania.

^a: Dr. McKenney has received speaking honorarium for AstraZeneca, KOS, Merck, and Pfizer and grant support from AstraZeneca, GSK, KOS, Merck, Pfizer, and Takeda, and has provided consulting services to AstraZeneca, KOS, Merck, Pfizer, and Sankyo.

^b: Dr. Bays, in over a decade of clinical research, has served as a clinical investigator for (and has received research grants from) pharmaceutical companies such as Abbott, Alteon, Arena, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Boehringer Mannheim, Bristol Myers Squibb, Esperion, Fujisawa, Ciba Geigy, GelTex, Glaxo, Genetech, Hoechst Roussel, KOS, Kowa, Lederle, Marion Merrell Dow, Merck, Merck Schering Plough, Miles, Novartis, Parke Davis, Pfizer, Pliva, Purdue, Reliant, Roche, Rorer, Regeneron, Sandoz, Sankyo, Sanofi, Searle, Shering Plough, SmithKline Beacham, Takeda, TAP, UpJohn, Upsher Smith, Warner Lambert, and Wyeth-Ayerst. He has also served as a consultant, speaker, and/or advisor to and for pharmaceutical companies such as AstraZeneca, Aventis, Bayer, Bristol Myers Squibb, KOS, Merck, Merck Schering Plough, Metabasis Therapeutics, Microbia, Novartis, Ortho-McNeil, Parke Davis, Pfizer, Roche, Sandoz, Sankyo, Sanofi Aventis, Shering Plough, SmithKline Beacham, Takeda, UpJohn, and Warner Lambert.

^c: Drs. Perevozkaya, Carlson, Davies, Mitchel, and Gumbiner are employees of Merck and may hold stocks or stock options in Merck.